QnAs with Rino Rappuoli.

From Edward Jenner’s breakthrough discovery in 1796 that inoculating an eight-year-old boy with cowpox sores protected him against smallpox, the field of vaccinology has come a long way. Today, vaccine design often begins with researchers scouring the DNA sequences of pathogens to exhume buried targets that might trigger a robust immune response in people. Once identified, such targets become the focus of vaccine development. To be sure, most licensed vaccines are still manufactured by laboriously growing large batches of entire pathogens or their parts in vats of animal cells or chicken eggs, which serve as vaccine factories. But that approach is slowly yielding to genome-guided methods. For example, efforts to target the relatively unchanging stalk of a protein on the surface of the flu virus have energized the search for a universal flu vaccine in recent years. Such a vaccine would render moot the virus’ notorious knack for evading the human immune system through constant mutation, and a handful of vaccine candidates are poised to enter clinical trials. Among the pioneers of the genome-guided approach to vaccine development is National Academy of Sciences member Rino Rappuoli, Chief Scientist at GlaxoSmithKline (GSK) Vaccines in Siena, Italy. At the 2016 Keystone Symposium on Translational Vaccinology for Global Health, Rappuoli traced the history of a new era in vaccine development that has come to be defined by undergirding advances in genetics and structural biology. Rappuoli spoke to PNAS about the long road to this new generation of vaccines.